The Epstein-Barr virus (EBV) has been studied extensively as a causative agent of some forms of human cancer. These investigations have included immunological studies on patients with EBV-associated cancers and on tumor tissues suspected to harbor the EBV genome. Such studies have resulted in the identification of antibodies to specific EBV antigens that are of diagnostic and prognostic importance in patients with EBV- associated diseases and in the identification of some of the antigens important in immunity to the virus-infected or transformed cells. Until recently, however, little was known about the composition of the different EBV antigen complexes. This laboratory has focused on the identification and characterization of the native polypeptides associated with the different EBV antigen complexes over the past 11 years through the support of this NCI grant. These studies have resulted in the identification of the major polypeptides associated with the EBV- induced membrane antigen (MA), viral capsid antigen (VCA) and early antigen (EA) complexes. These polypeptides have been mapped to specific fragments of EBV DNA and the biological activity associated with some of these polypeptides has been identified. Monoclonal antibodies have been generated to all of the polypeptides which have been used by numerous investigators working on EBV. The specific aims of this renewal proposal for years 12-16 are: (1) to continue to identify and fully characterize polypeptides associated with each of these major antigen complexes and to utilize the purified polypeptide in different immunological studies; (2) to attempt to determine the importance of polypeptides associated with these different antigen complexes in the induction of T-cell immunity against the virus-infected or transformed cell; (3) to continue to determine if the prognostic importance of antibody measured by the ADCC is assay related to the presence of IgA antibodies to specific epitopes expressed on the major MA glycoprotein; (4) to perform ultrastructural studies to determine the biological significance of the cytoplasmic filamentous structures associated with the restricted (R) component of the EA complex; and (5) to continue to collaborate with other investigators using our monoclonal reagents. Completion of these studies will lead to a better understanding of the nature of the viral proteins important to the development of both humoral and cellular immunity to the virus- infected and transformed cells and could lead to the development of new approaches for the prevention or treatment of EBV- associated diseases.